Transsphenoidal surgery is the usual treatment of choice for adrenocorticotropic hormone-secreting pituitary adenomas associated with Cushing's disease. In this paper the authors investigate the complications of transsphenoidal surgery in the treatment of a contemporary series of patients with Cushing's disease. Between January 1992 and December 1997, 105 patients with Cushing's disease underwent transsphenoidal surgery at the University of Virginia Health Sciences Center. A retrospective analysis of the complications was conducted, and the mortality rate was found to be 0.9% and permanent morbidity was 1.8%. The overall number of complications was 14 (13.3%), which included seven complications directly related to surgery; one instance of permanent diabetes insipidus; one syndrome of inappropriate secretion of antidiuretic hormone; and five medical complications (four patients developed deep vein thrombosis and one developed pneumonia). Transsphenoidal surgery for Cushing's disease has a higher complication rate than that for pituitary adenomas in general. This is primarily related to a greater number of medical complications, most notably deep vein thrombosis, resulting from the generally debilitated state of most patients with Cushing's disease. In view of the high incidence of deep vein thrombosis in these patients, prophylaxis for thromboembolism during the perioperative period is recommended.